IntroductionRheumatoid arthritis (RA) is one of the most commonly encountered autoimmune diseases. Treatment generally includes disease-modifying anti-rheumatic drugs (DMARDs) and/or biological therapy. However, a significant proportion of the patients do not respond to treatment either as a (primary failure) or lose efficacy over time (secondary failure). Several factors are assumed to influence these conditions. ObjectivesTo estimate the prevalence of failure of biological therapy in patients with RA and its causes. MethodsA total of 335 RA patients who were diagnosed at a tertiary center in Jeddah, Saudi Arabia, and had a failure after receiving biological therapy were included in this study. Several variables were considered; patient's socio-demographic data, comorbid conditions, types of biological therapy, the duration of using biological therapy in months, number of biological therapies, allergic reactions, disease activity, and treatment duration. ResultsOverall the prevalence of failure to biological therapy was 58%; 77% primary failure and 23% secondary failure. Patients with negative rheumatoid factor (RF) (p=0.006), using low-dose steroids, and with a longer disease duration had a significant failure of biological therapy (p=0.023). ConclusionA high percentage of RA patients had a failure of biological therapy. A multicentric trial is recommended to look for additional factors.